Two surveys have been conducted on behalf of the
Campylobacter Working Group with the aim of assessing the feasibility
of a European network on human Campylobacter infections. The first survey,
conducted in 18 countries, collected information about diagnostic methods
used for surveillance purpose while the second one, conducted among 10
European countries, gathered data on diagnostic methods and procedures
in primary laboratories. Seventeen of the 18 countries had a surveillance
system for Campylobacter infections and 13 a national reference laboratory.
The case definition used for the surveillance in all these countries included
laboratory confirmation. No commonly applicable subtyping methods were
applied. Concerning primary laboratories dealing with Campylobacter infections,
only a few of them reported directly to the national level, and antimicrobial
susceptibility testing was performed by about half of the laboratories.
These surveys indicated that a basic infrastructure for a wide European
Campylobacter surveillance exists.

Introduction
In the late 1970s, the development in Campylobacter isolation techniques
resulted in enhanced detection of Campylobacter infections. Since then,
thermotolerant Campylobacter species Campylobacter jejuni and Campylobacter
coli have been included amongst the most important causative agents
of acute diarrhoea in the industrialised world (1). The reported numbers
of campylobacteriosis are increasing in many European countries, revealing
that these infections are emerging and becoming a major public health
problem in Europe (2). Campylobacter is among the diseases for which
a European-wide surveillance has been decided (Commission Decision 2000/96/EC).
However, at this time, no information on the tools and schema used to
diagnose Campylobacter infections or surveillance systems for human
campylobacteriosis on local and national levels in European countries
was available. To assess the feasibility of a European network on human
Campylobacter infections, two surveys were conducted. The first survey
collected the information about the diagnostic methods and procedures
in national reference centres as well as the existing surveillance systems
among 18 European countries. The second survey obtained information
about diagnostic methods and procedures in primary laboratories that
investigate patient samples among 10 European Union (EU) countries.
The project, supported by the European Commission (DG SANCO) (3), has
been conducted by the Robert Koch-Institut (RKI) in Berlin. Partners
from national public health institutes and European networks, Enternet
and Campynet, cooperated on the project.

MethodsSurvey 1
This survey concerned the National Reference Laboratories (NRLs) and
Surveillance systems from the 15 Member States, Norway, Iceland and
Switzerland. It focused on the following aspects:
- Existence of NRLs, tasks of NRLs, methods for Campylobacter isolation,
identification and molecular sub-typing, quality assurance and accreditation
(4).
- Surveillance systems (statutory/sentinel), case definitions, other
data sources, reported numbers of cases, recorded outbreaks.Survey 2
All countries willing to participate (10) were included in the second
survey. These countries were Austria, Denmark, Finland, France, Germany,
Greece, Republic of Ireland, Italy, Portugal and the United Kingdom
(UK). The questionnaire was tested in five countries (France, Germany,
the UK, The Netherlands, Republic of Ireland) by 14 laboratories before
final revision. The following information was collected:
A. Basic information (type of laboratory, patient groups, total number
of investigations, sample transport, routine methods for testing, submitted
patient information)
B. Sample handling and culture practices (published method, time interval
between sampling and cultivation, procedures before cultivation, cultivation
practices, plate preparation and quality control, confirmation and typing
methods, storing and sending isolates, reporting, antimicrobial susceptibility
testing).
C. External quality assurance (participation, accreditation).
The questionnaire was translated into French (Institut de Veille Sanitaire),
German (Robert Koch-Institut) and Italian (Istituto Superiore di Sanità).
The data entry of the French questionnaires was performed in France
and the data were added to the total database in Berlin. Epi Info 6.04
and SPSS 10.07 were used for data analyses.

Results and discussion
Campylobacter surveillance systems in Europe
Of 18 countries that responded to the first survey, 17 had developed
a surveillance system for Campylobacter infections (figure). Nine countries
had a statutory system and seven countries had a sentinel system which
covered only part of the population. One country had both systems.
The reporting partners were physicians, laboratories, local health authorities
and hospitals. In nine countries, the laboratories were the only notifying
partners among both statutory and sentinel systems. In one country,
the physicians were the only notifying partners in the statutory system.
In the other countries, at least two partners reported the cases. At
national level, national public health institutes (NPHI) collected the
surveillance information in 14 countries, and NRLs in three countries.
At European level, the main information flow was thus from the laboratories
and physicians to the NPHIs. In 14 countries (82%), the information
was forwarded as single cases.

Ten out of 17 countries had developed case definitions for Campylobacter
surveillance. All included laboratory confirmation into the case definition
but other criteria varied between the countries. At the European level,
the facts to be considered for a case definition would be the inclusion/exclusion
of an asymptomatic case and cases that are epidemiologically linked
to a laboratory confirmed case (e.g. in outbreaks).
Demographic information about age and sex is most frequently (15/16
countries, no data available from Greece) transmitted to surveillance
centres in statutory and sentinel systems. Travel history is routinely
forwarded in nine countries. Five countries collect also the information
about possible risk factors. Information about the suspected source
of infection is submitted in six countries.

Trends of Campylobacter infections in Europe
Fifteen out of 18 countries reported 134 971 Campylobacter infections
in 1999. Based on reported numbers, the notifications / 100 000 inhabitants
ranged from 2.9 to 166.8 between countries in 1999. In 1998, the mean
number of notifications / 100 000 inhabitants in the EU (n=15) was 61
(95% CI 47 - 78) and in 1999 it was 71 (95% CI 56 - 90). The increase
in notifications was thus about 16% between 1998 and 1999.
During the five year period from 1995 to 1999, 11 countries reported
154 outbreaks. The highest number of reported outbreaks was in 1997.
As the reporting of outbreaks varied greatly by country, however, the
numbers are only a rough estimate of the true situation. In 48% of the
reported outbreaks, food was the likely vehicle of transmission. For
15%, consumption of unpasteurised milk was reported as the source of
infection and another 15% were waterborne. In every fifth outbreak (21%),
the cause remained unknown or was not reported. An analytical epidemiological
study (case-control or cohort study) was carried out in 14% of the reported
outbreaks.

National reference laboratories for Campylobacter in Europe
In the survey among 18 European countries, 13 countries reported having
a national reference laboratory (NRL) or a laboratory performing reference
tasks (later referred as a NRL). The most commonly mentioned tasks of
NRLs were: confirmation of results of primary laboratories (n=12), development
of new typing (n=10) and analytical (n=9) methods, development of proposals
for standardisation of methods (n=9) and conduction of training courses
(n=7). In seven countries, the NRLs carried out also a routine primary
investigation for Campylobacter from stool samples. Although 12 NRLs
(92%) reported confirming the results of primary laboratories, only
about 13% (range 6% - 100%) of primary laboratories in Europe reported
sending the isolated strains routinely or occasionally to the NRLs for
confirmation or further characterisation. This indicates that in most
countries the strains are not collected centrally by the NRLs.
There exists no commonly applicable method to subtype Campylobacter
strains. Serotyping with commercial antisera is possible, but not all
strains are typeable with commercial antisera. NRLs in four countries
serotyped the strains routinely according to the modified Penner scheme.
Phage typing was used in the UK only. Antimicrobial resistance patterns
were used as a typing method in eight NRLs. The genotyping methods varied
between the countries and one NRL may use several molecular subtyping
methods. Direct DNA based analyses of chromosomal or extrachromosomal
genetic elements were performed in 9 countries. Of these, pulsed field
gel electrophoresis (PFGE) was used in 8 countries. PCR based profiling
was performed in 7 countries.

Campylobacter diagnosis and reporting from primary laboratories in Europe
A total of 1014 (41%, range 17-92%) primary laboratories from 10 EU
countries responded to the survey. Of these, 622 (61%) performed primary
Campylobacter diagnosis (table). Taking into account the infrastructures
and information available in each country, the results were considered
representative, even though the sampling methods and response rates
varied between countries.
As the target group in some countries was not easy to determine, the
survey, at first, also included laboratories that did not perform Campylobacter
diagnostics. This was the case in Germany. In the UK for example, the
laboratories are a sub sample of laboratories belonging in the national
sentinel surveillance system. They had gone through an assessment before
inclusion in the national sentinel surveillance system. Most of the
Campylobacter laboratories were either hospital based (53%, range 27%
-100%) or private laboratories (41%, range 0-72%). The private laboratories
played a major role in France and Germany.
In European primary laboratories, the method for isolation and confirmation
of Campylobacter from stool samples was principally the same. However,
the mean number of positive tests/100 tested samples (mean isolation
rate) varied from 2.2 - 6.2 between the countries indicating that there
are significant differences in investigation routines and/or methods
used to culture Campylobacter. In three countries, all stool samples
were tested for Campylobacter. In these countries, the primary laboratories
were more likely to have an isolation rate >4.00 (>4 positive
results per 100 samples tested for Campylobacter) (OR 4.4, 95% CI 1.6
- 12.1) indicating that routinely performed Campylobacter investigation
may yield to better isolation rate. In the other seven countries, the
ratio between incoming stool samples and performed Campylobacter investigations
was about 2:1 in 1999.
Principally, the laboratories reported positive findings via the local
health authorities to the national level. At European level, only few
primary Campylobacter laboratories reported their positive findings
directly to the national surveillance centre (10%) or the NRL (4%).
In only three countries did over 80% of primary laboratories report
directly to the national surveillance centre.

Quality assurance in Campylobacter diagnostic
The NRLs in six countries (46%) reported having internal quality assurance
procedures e.g. media control and monitoring the growth conditions.
About half of primary Campylobacter laboratories (47%) reported controlling
the quality of media. Laboratories that prepared the agar plates themselves
also controlled the quality of plates (Spearman rs=0.88, p<0.01).
NRLs in four countries reported having EQA (external quality assurance)
to control their diagnostic performances and six NRLs planned to adapt
an EQA system. Of primary Campylobacter laboratories, 44% reported participating
in EQA schemes for Campylobacter culturing in their country. However,
many laboratories (40%) did not know if there were EQA schemes available
in their country. This indicates that information about the EQA schemes
available in Europe should be better disseminated among laboratories.
Antimicrobial susceptibility testing
About half of primary Campylobacter laboratories (46%) reported always
performing antimicrobial susceptibility testing. Most frequently, the
susceptibility for erythromycin (92%) and ciprofloxacin (83%) was tested.
The NRLs in 12 countries reported performing antimicrobial susceptibility
testing for Campylobacter. Usually, the susceptibility for nalidixic
acid and cephalotin was used for species differentiation whereas the
susceptibility for ciprofloxacin and erythromycin was used for clinical
purposes. Among those laboratories that performed susceptibility testing
for Campylobacter, agar diffusion method was routinely used in most
NRLs (67%, n=12) and primary Campylobacter laboratories (85%, n=342).

Conclusion
The results of the surveys indicate that a basic infrastructure for
a European wide Campylobacter surveillance exists. Almost all EU countries
have developed a national surveillance system for Campylobacter. Most
countries receive the notifications as single cases enabling an efficient
data analysis. Many countries receive travel information on a routine
basis within their surveillance systems making it possible to assess
travelling as a risk factor for a country.
Although it appears that the reported number of outbreaks has declined
since 1997, it may not reflect the actual situation, because very few
countries systematically collect data from outbreaks. The low percentage
of performed epidemiological studies indicates a strong need for epidemiological
training and leaves doubts on the evidence of reported vehicle. However,
the total number of reported cases is increasing yearly in many European
countries. There is a need to make joint efforts to stop the increase
and determine the risk factors with joint epidemiological investigations.
The diagnostic procedure is principally the same throughout Europe at
local, national and international levels, but there is evidence of significant
differences in methodological procedures that should be studied further.
Contact between national and local laboratories appears to be relatively
rare. In some countries, however, the cooperation between national and
local level functions well.
There is a strong need for a standardised molecular sub-typing method
which would be applicable in many countries. These methods could be
used to detect international outbreaks and links between apparently
sporadic cases. As the Campynet group has been working to achieve this
goal, this group's results should be taken into account in network planning.
Antimicrobial susceptibility testing methods were basically the same
in most countries both at local and national levels. This provides a
good basis for the surveillance of antimicrobial resistance patterns.

Recommendations
As the trends of human Campylobacter infections show increasing numbers,
and a good basic infrastructure for Campylobacter surveillance exists
in almost all EU countries, it is strongly recommended to implement
an EU-wide surveillance network1. At first, the network should aim to
standardise the collection of data and then develop the network step
by step. Since in most of the countries data are available at the National
Surveillance Centres, they should be the national contact points in
the network. Countries with no surveillance or with mixed surveillance
systems should be supported to organise and build up their systems in
a way that produces comparable data. The collection of data from outbreaks
and antimicrobial resistance should be incorporated into the surveillance
from the beginning. To achieve this, the epidemiological and methodological
training both on national and international level should be strengthened
in Europe. At some point, a European-wide epidemiological study could
be performed. As Campylobacter infections are zoonoses, good cooperation
between physicians, veterinarians and epidemiologists is essential for
a successful surveillance network. The network should have cooperational
ties to expert groups such as Campynet and the Community Reference Laboratory
for the Epidemiology of Zoonoses. Countries should be encouraged to
collect travel history information routinely, in order to obtain information
on travelling as a risk factor at Community level.
In many countries, the interaction between primary laboratories and
NRLs should be improved. NRLs should actively offer primary Campylobacter
laboratories the information about diagnosis and quality assurance procedures.
The laboratories, both at local and national levels, should be encouraged
to consider carefully the need to control the different steps in their
diagnostic procedures and the need for adopting an EQA system.

1 Note: no European Network for Campylobacter surveillance has been
implemented so far. Enternet has made a proposal to add Campylobacter
surveillance into current activities which has been accepted in principle
by the European Commission. Until such time as there is a microbiological
typing method of choice in place surveillance under Enternet will remain
at a low level of activity. However, the European Centre for Disease
Control and Prevention should be established in the near future and
it could help in coordinating to build up European wide surveillance
networks.

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